Is Congress Mistakenly Loosening the Regulation of New Drugs and Medical Devices?

by Kelly McBride Folkers and Alison Bateman-House

Kelly McBride Folkers is a research associate in the New York University School of Medicine’s Division of Medical Ethics, and she is pursuing a master’s degree in bioethics from the New York University Center for Bioethics. Alison Bateman-House is an assistant professor in the New York University School of Medicine's Division of Medical Ethics, where she works on issues related to the ethics and history of human subjects research and public health.

Remember Thalidomide?

Pack of Thalidomide tablets c.1960 Wikipedia

At a time when bipartisan policymaking seems endangered, the 21st Century Cures Act stands out. An expansive $6.3 billion health reform bill that would, among other things, add funding to programs like the cancer “moonshot” and precision medicine initiatives and amend Food and Drug Administration (FDA) standards for regulating drugs and medical devices, the Act passed the Senate and House of Representatives by an overwhelming margin.

Cures has been described by experts as a “Christmas tree,” packed with disparate measures intended to garner support from across the political spectrum. While many provisions, such as those addressing opioid abuse and the development of new antibiotics, are undoubtedly good for the health of the country, the Act has drawn strident opposition from Senate progressives like Elizabeth Warren and Bernie Sanders. Their concerns, as well as those of former FDA officials and national consumer groups, surround Cures’ provisions for lowering the standards for FDA approval of certain drugs and medical devices. Warren, who proclaimed that the Cures Act had been “hijacked” by the pharmaceutical industry, is one of many critics who fear the Act could result in unintended but foreseeable harm to patients.

Reasonable minds can argue about how and whether the language in the Cures Act –compromises hammered out over two years - sets the stage for harm to patients.

But what is undeniable is that over the years, the United States has swung between looser and stricter regulation of medical products and Cures continues an ongoing pendulum swing away from the strict regulation of new drugs and devices.

The Pure Food and Drug Act of 1906 paved the way for the creation of the FDA, but it wasn’t until 32 years later that the agency gained the authority to oversee the safety of food and drugs. This reform was prompted by the death of more than 100 patients when the manufacturer of sulfanilamide, an antibacterial agent, prepared the drug with the toxic solvent diethylene glycol. Twenty-four years later, in 1962, came another reform born of scandal. Use of the FDA-unapproved drug thalidomide as a treatment for morning sickness resulted in severe birth defects in the children exposed to the drug in utero. The injury of these children spurred passage of the Kefauver-Harris amendments to the Food, Drug, and Cosmetic Act, among the results of which was the creation of the current three-stage clinical trial system for developing new drugs.

The first stage of clinical testing, Phase 1, is when a novel drug is first used in humans, normally healthy volunteers. The drug is given in increasing amounts in an effort to determine at what dose side effects become unacceptable. In Phase 2 of clinical testing, the drug is given to patients with the condition for which the drug is being developed to determine whether the drug is effective and to see what side effects occur. If the Phase 2 findings are promising, the drug moves to Phase 3, in which it is compared against either the standard treatment for the condition or, in certain cases, a placebo, for the purpose of determining how the drug performs in terms of effectiveness and safety.

Over time, these three distinct phases have become elided, creating a bewildering mix of, for instance, Phase 1b trials that are essentially Phase 2 trials and so on. And over time, largely due to patient advocacy efforts that began during the AIDS epidemic, the FDA has increasingly considered allowing approval without requiring the completion of all three phases of clinical testing. For example, for serious, life-threatening conditions where there are no therapies, the agency has created an “accelerated approval” pathway by which it may approve drugs on the basis of Phase 1 and 2 data, with the caveat that approval can be revoked if a mandated post-approval phase 3 trial does not prove safety and efficacy. Indeed, the FDA did just this when it revoked the approval of Avastin for use in breast cancer after Phase 3 data indicated the drug did not slow the progression of metastatic breast cancer but that its use did result in severe adverse effects such as dangerously high blood pressure and hemorrhaging.

Many patient advocates and pharmaceutical lobbyists — more than 1,300 of them — view the Cures Act as necessary to get the newest, best treatments to market faster. For those in need, new therapies and, yes, cures cannot come soon enough, and they blame the FDA for obstructing the development of these treatments, despite the fact the agency approves drugs faster than similar regulatory agencies around the world. But accelerating the pace of drug development will inevitably increase risk. In a time when we are very aware of the pain, suffering, and foreshortened lives of patients (and indeed, the trials and travails of being a patient are publicized both by patient advocacy organizations and the pharmaceutical industry), it may seem reasonable to sacrifice a bit of security for speed. Yet it was not that long ago that policymakers thought it made sense to create a regulatory process that would ensure safety and efficacy, even if that meant the imposition of a three-part clinical trial process that would inevitably lengthen the time it took to bring new drugs to market.

As happens all too often in health policy reform, Congress mandated high standards of evidence for drug approval only after patients experienced significant harms, even death. Let us hope that this latest move of the pendulum toward speed and away from safety does not result in such outcomes.